Adenosine diphosphate ribosyl transferase (ADPRT) and unscheduled DNA synthesis (UDS) are inter-related measures that may be obtained in mononuclear leukocytes from venous blood. They reflect DNA repair, and are affected by pro-oxidant states. Both measures have been inversely related to cancer and to cancer prone individuals. The inverse relationships of ADPRT to cancers of the lung, colon and breast have been quite strong. For example, for breast cancer, adjusted odds ratios in the three lowest quintiles of ADPRT were 10 to 14. These results suggest high relative risk for etiologic processes involving more than half of all breast cancers. In these studies, ADPRT measures have been done from venous blood, with isolation of an individual' mononuclear leukocytes and then reconstitution with plasma from the same individual. It is unclear whether the inter-individual variability and apparent cancer susceptibility originate in the individual's cells or in th individual's plasma. The new study continues the general design of NIH grant CA 50326 on breast cancer and these measures. The new study involves 432 postmenopausal women 144 women with breast cancer and 288 controls (144 with benign breast disease; 144 without benign breast disease). Each participant will have 3 assays done simultaneously: #1. the usual ADPRT (patient's cells with patient's plasma), #2. the variable cell ADPRT (patient's cells with standardizing plasma), an #3. the variable plasma ADPRT (standardizing cells with patient's plasma). The primary analysis will test for the ability of each measure to distinguish cancer cases from controls. Other analyses will compare inter- individual variability for each of the three assays. The study meets the Award's criteria of "...developing or validating a laboratory...procedure with potential for improving the quality of cancer epidemiologic research". These investigations will lead to a more accurate cancer susceptibility measure, a clearer knowledge of biologic mechanisms, and ultimately to the technology that will facilitate longitudinal research